Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD 404

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

as of 1981

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Menthyl lactate

IUPAC Name:

Menthyl lactate

Constituent 2

Reference substance name:

Methyl lactate

EC Number:

208-930-0

EC Name:

Methyl lactate

Cas Number:

547-64-8

IUPAC Name:

methyl 2-hydroxypropanoate

Constituent 3

Reference substance name:

Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-

EC Number:

612-179-8

Cas Number:

61597-98-6

Molecular formula:

C13H24O3

IUPAC Name:

Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-

Test material form:

other: white solid

Details on test material:

- Name of test material (as cited in study report): 90/620105

Test animals

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Møllegaard Breeding Centre ApS, Ejby, Skensved, Denmark
- Age at study initiation: not reported
- Weight at study initiation: 1800 to 2700 g
- Housing: individually in PPL cages, 45 x 55 cm, with perforated floor
- Diet (e.g. ad libitum): Altromin 2123, Chr. Petersen A/S, Ringsted, Denmark ad libitum
- Water (e.g. ad libitum): fresh water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 6
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours light

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: mixture of ethanol 96% and diethylphthalate (1:1)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of moistened test material
- Concentration (if solution): 50%, 10% and 1% by weight

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL of test solution, i.e. test substance dissolved in a mixture of ethanol 96% and diethylpthalate (1:1)

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: the test substance was applied to two anterior, two posterior and one centrally located site
- % coverage: not reported
- Type of wrap if used: treatment sites were covered with gauze packs that were secured with adhesive tape and fixed with Scanpore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was cleaned with soap and lukewarm water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injury in depth): 4

No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm, extending beyond area of exposure): 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours after removal

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours after removal

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours after removal

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours after removal

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours after removal

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours after removal

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 7

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours after removal

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 8

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours after removal

Score:

0

Max. score:

4

Results 9

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours after removal

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Results 10

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours after removal

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 11

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours after removal

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 12

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours after removal

Score:

0

Max. score:

4

Irritant / corrosive response data:

None of the animals treated with 100% showed an erythema or oedema score that would trigger classification. The scores for erythema and oedema formation were slightly higher for the test sites treated with 50% in a mixture of ethanol 96% and diethylphthalate (1:1), however, scores were not triggering classification at a test concentration of 50%. Corrosiveness to the skin was not observed. After the observation period of 14 days, few animals had sites with scattered small white scales, but the underlying skin was intact. All effects were considered to be fully reversible within 14 days.

Other effects:

No effects observed

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was not irritating to the rabbit skin when tested purely or in dilution. All effects observed at observation time points at 24, 48 and 72 hours after patch removal were fully reversible within a period of 14 days.

Executive summary:

The skin irritation potential of the test substance menthyl lactate was studied under GLP in accordance with OECD TG 404. The pure substance (wetted with the vehicle ethanol 96%:diethylphthalate, 1:1) or dilutions of the test substance in the vehicle at 50%, 10% and 1% were applied for four hours under occlusion to five sites on the clipped, intact skin of six female rabbits of the stock Mol:Russian (1800 to 2700 g). After patch removal the skin was washed with soap and water. Animals were then observed for a period of 14 days and scorings of the skin were made at 24, 48 and 72 hours after patch removal. The substance or its dilutions were not corrosive to the rabbit skin. None of the individual mean scores for erythema or oedema were above 2 with the neat substance or above 2.33 with the 50% dilution. All observed effects were fully reversible within the observation period of 14 days. The substance therefore was considered to be not irritating to the rabbit skin.